The biochemical basis of cell-substrate adhesion remains to be elucidated. Evidence has recently accumulated to implicate the plasma protein von Willebrand factor (vWF) in the adhesion of platelets to components of the vascular subendothelium including collagen. This vWG-dependents adhesive process is an essential element of normal primary hemostasis, has been implicated in the pathogenesis of atherosclerosis and is defective in von Willebrand's disease. Recent studies by this investigator have demonstracted a direct interaction between vWF and fibrillar collagen. The proposed studies will define the biochemical basis and specificity of this important interaction by examination of the binding of purified vWF to fibrillar collagen and to surfaces coated with various forms of collagen in addition to noncollagenous proteins. The biochemical nature of this interaction will be further examined by chemical modification of both vWF and collagen. The collagen binding activities of vWF and fibronecting another plasma protein implicated in cell-substrate adhesion will be compared by direct and competitive binding assays using fibrillar collagen and tissue culture dishes coated with various forms of collagen. Proteolytic fragments of vWF will be prepared, purified and then examined for platelet and collagen binding activities to identify discrete collagen and platelet binding domains. The fragments with binding activities will the be tested for effect in assays of vWF activity (Ristocetin cofactor) and plateletcollagen, in a manner analagous to fibronectin, by factor XIIIa will be examined. These studies will explore the chemical nature of the vWF-collagen interaction. The findings will increase our understanding of both normal and abnormal hemostatic mechanisms. The concepts which evolve should be of general importance to our understanding of the function of cell-substrate adhesion factors.